Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative and structural genetic alterations cause the development and progression of prostate cancer. A number of genes have been implicated in prostate cancer by genetic alterations and functional consequences of the genetic alterations. These include the ELAC2 (HPC2), MSR1, and RNASEL (HPC1) genes that have germline mutations in familial prostate cancer; AR, ATBF1, EPHB2 (ERK), KLF6, mitochondria DNA, p53, PTEN, and RAS that have somatic mutations in sporadic prostate cancer; AR, BRCA1, BRCA2, CHEK2 (RAD53), CYP17, CYP1B1, CYP3A4, GSTM1, GSTP1, GSTT1, PON1, SRD5A2, and VDR that have germline genetic variants associated with either hereditary and/or sporadic prostate cancer; and ANXA7 (ANX7), KLF5, NKX3-1 (NKX3.1), CDKN1B (p27), and MYC that have genomic copy number changes affecting gene function. More genes relevant to prostate cancer remain to be identified in each of these gene groups. For the genes that have been identified, most need additional genetic, functional, and/or biochemical examination. Identification and characterization of these genes will be a key step for improving the detection and treatment of prostate cancer.
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PMID:Prevalent mutations in prostate cancer. 1626 36

Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includes ex vivo corrective therapy, suicide, and antisense therapy.
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PMID:Molecular biology in prostate cancer. 1664 13

Prostate cancer is one of the most common cancers among men and has long been recognized to occur in familial clusters. Identification of genetic susceptibility loci for prostate cancer has however been extremely difficult, and only in 1996 was the first prostate cancer susceptibility locus HPC1 mapped to chromosome 1q24-25. Since, several additional putative loci have been identified by genetic linkage analysis on chromosome 1, 17, 20 and X (reviewed in). For three of these loci, family-based studies have identified three genes associated with inherited prostate cancer: the 3' processing endoribonuclease ELAC2/HPC2 gene, the macrophage scavenger receptor 1 gene (MSR1), and the endoribonuclease RNase L gene (RNAse L/HPC1). Here we will focus our review on the RNAse L gene and its involvement in prostate cancer and other diseases.
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PMID:Involvement of the RNAse L gene in prostate cancer. 1686 93

RNA-degradation is one of the fundamental mechanisms of interferon (IFN)-inducible antiviral response in mammalian cells. This is primarily brought about by the IFN-inducible 2',5'-oligoadenylate (2-5A)-cofactor dependent ribonuclease L (RNase L). RNase L also functions as a tumor suppressor gene in case of prostate cancer due to its role in apoptosis. We report that RNase L is induced by stress-inducing agents such as double-stranded RNA [poly(I:C)], chemotherapeutic drugs, hydrogen peroxide (H(2)O(2)), calcium chloride (CaCl(2)) and tumor necrosis factor-alpha (TNF) in the human cervical carcinoma (HeLa) cells. The level of RNase L was not detected in the untreated cells. Induction of RNase L by such stress-inducing agents correlated with degradation of cellular RNA, fragmentation of chromatin-DNA and induction of apoptosis. We checked the stress-inducible transcription factor, nuclear factor kappa B (NF-kappaB), which was persistently activated by cycloheximide but not by other agents after 24 hours indicating no role of NFkappaB in the RNase L-induction. However, as expected, TNF-induced NF-kappaB activity was stimulated within 10-30 minutes through degradation of IkappaB-alpha. Our results strongly suggest that the IFN-inducible RNase L is induced by a broad range of stress-inducing signals such as double-stranded RNA (dsRNA) produced during viral infection, membrane- and osmotic shock caused by CaCl(2) and oxidative stress induced by H(2)O(2), inflammation stimulated by TNF-alpha and chemotherapy. Thus, in addition to its antiviral function, the IFN-inducible RNase L may play an important role during stress-response through RNA-degradation and apoptosis.
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PMID:Induction of the interferon-inducible RNA-degrading enzyme, RNase L, by stress-inducing agents in the human cervical carcinoma cells. 1720 Jun 14

Genetic susceptibility to prostate cancer has been consistently observed by a large number of studies. Recently, several pieces of evidence obtained from epidemiological and pathological studies support that chronic inflammation in prostate tissues may play a role in prostate cancer development. Multiple genes that play critical roles in inflammatory pathways have been associated with prostate cancer risk. In this article we review the key genetic findings of the associated genes. This includes 2 genes identified through family studies, ribonuclease L (RNASEL) and macrophage scavenger receptor 1 (MSR1), as well as a number of genes suggested by case-control studies, such as macrophage inhibitory cytokine-1 (MIC-1), interleukins (IL-8, IL-10), vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM), and Toll-like receptors (TLR-4, TLR-1-6-10 gene cluster). Overall, recent studies seem to suggest multiple genes work together to increase prostate risk, and this is consistent with the reality that inflammation is a very complex process. Thus, future studies are expected to place an emphasis on the study of gene-gene interactions. Advances in high throughput genotyping, data mining, and algorithm development are needed in order to produce interpretable results.
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PMID:Genetic variability in inflammation pathways and prostate cancer risk. 1748 24

We conducted a genome-wide association study of 3090 sporadic prostate cancer patients and controls using the Affymetrix 10 000 SNP GeneChip. Initial screening of 40 prostate cancer cases and 40 non-cancer controls revealed 237 SNPs to be associated with prostate cancer (P<0.05). Among these SNPs, 33 were selected for further association analysis of 2069 men who had undergone a cancer-screening prostate biopsy. Results identified five loci as being significantly associated with increased prostate cancer risk in this larger sample (rs 1930293, OR=1.7, P=0.03; rs 717809-2p12, OR=1.3, P=0.03; rs 494770-4q34, OR=1.3, P=0.01; rs 2348763-7p21, OR=1.5, P=0.01; rs 1552895-9p22, OR=1.5, P=0.002). To validate these association data, 61 additional HapMap tagSNPs spanning the latter five loci were genotyped in this subject cohort and an additional 1021 men (total subject number=3090). This analysis revealed tag SNP rs 4568789 (chromosome 1q25) and tag SNP rs 13225697 (chromosome 7p21) to be significantly associated with prostate cancer (P-values 0.009 and 0.008, respectively). Haplotype analysis revealed significant associations of prostate cancer with two allele risk haplotypes on both chromosome 1q25 (adjusted OR of 2.7 for prostate cancer, P=0.0003) and chromosome 7p21 (adjusted OR of 1.3, P=0.0004). As linkage data have identified a putative prostate cancer gene on chromosome 1q25 (HPC1), and microarray data have revealed the ETV1 oncogene to be overexpressed in prostate cancer tissue, it appears that chromosome 1q25 and 7p21 may be sites of gene variants conferring risk for sporadic and inherited forms of prostate cancer.
Prostate Cancer Prostatic Dis 2008
PMID:A genome-wide association screen identifies regions on chromosomes 1q25 and 7p21 as risk loci for sporadic prostate cancer. 1787 39

The 2-5A/RNase L pathway is one of the first cellular defences against viruses. RNase L is an unusual endoribonuclease which activity is strictly regulated by its binding to a small oligonucleotide, 2-5A. 2-5A itself is very unusual, consisting of a series of 5'- triphosphorylated oligoadenylates with 2'-5' bonds. But RNase L activity is not limited to viral RNA cleavage. RNase L plays a central role in innate immunity, apoptosis, cell growth and differentiation by regulating cellular RNA stability and expression. Default in its activity leads to increased susceptibility to virus infections and to tumor development. RNase L gene has been identified as HPC1 (Hereditary Prostate Cancer 1) gene. Study of RNase L variant R462Q in etiology of prostate cancer has led to the identification of the novel human retrovirus closely related to xenotropic murine leukemia viruses (MuLVs) and named XMRV.
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PMID:[RNase L, a crucial mediator of innate immunity and other cell functions]. 1895 May 83

Prostate Cancer (CAP), is a complex disease with a multifactorial origin. It is characterized by heterogenous patterns of growth of neoplasic tissue, varying widely in its progression, age of beginning and therapy response. It is considered as the second most common cause of death by cancer in men and, it has been estimated, that one of five, suffers of CAP through the course of his life. The genetic etiology of neoplasic transformation of normal prostate cells is still not known; nevertheless, investigations in epidemiology have demonstrated a strong genetic component in its development, suggesting so much a pattern of mendelian inheritance as the presence of loci of susceptibility throughout the human genome. It has been described a cromosomic location related to the CAP in locus 1q24-25, denominated HPC1, where the gene RNASEL is located, and the seggregation of its alleles has been associated with the development of CAP in numerous familiar groups. The RNASEL gene codifies for a ribonuclease protein that degrades vi-ral and cellular ARN and takes part in the apoptosis. A decrease of the enzymatic activity up to three times in carriers of the G1385A polymorphism of this gene has been reported, and the same has been associated frequently with the development of CAP. Using a variant of the Polymerase Chain Reaction, Allele specific amplification, this investigation had as objective to determine the association between variant G1385A and CAP, in a sample of 103 masculine individuals with and without CAP, pertaining to the population of Maracaibo, Venezuela. An association between these variants and CAP could not be demonstrated.
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PMID:[G138A polymorphism of the RNASEL gene and its association with the development of prostate cancer. Preliminary study]. 1996 Oct 52

Three genes, namely, ELAC2 (HPC2 locus) on chromosome 17p11, 2'-5'-oligoisoadenlyate-synthetase-dependent ribonuclease L (RNASEL, HPC1 locus), and macrophage scavenger receptor 1 (MSR1) within a region of linkage on chromosome 8p, have been identified as hereditary tumor suppressor genes in prostate cancer. We genotyped 41 tagged single nucleotide polymorphisms (SNPs) covering the three genes in a case-control cohort, which included 1,436 Caucasians, 648 Hispanics, and 270 African Americans. SNPs within MSR1, ELAC2, and RNASEL were significantly associated with risk of prostate cancer albeit with differences among the three ethnic groups (P = 0.043-1.0 x 10(-5)). In Caucasians, variants within MSR1 and ELAC2 are most likely to confer prostate cancer risk, and rs11545302 (ELAC2) showed a main effect independent of other significant SNPs (P = 2.03 x 10(-5)). A major haplotype G-A-C-G-C-G combining five SNPs within MSR1 was further shown to increase prostate cancer risk significantly in this study group. Variants in RNASEL had the strongest effects on prostate cancer risk estimates in Hispanics and also showed an interaction effect of family history. In African Americans, single SNPs within MSR1 were significantly associated with prostate cancer risk. A major risk haplotype C-G-G-C-G of five SNPs within ELAC2 was found in this group. Combining high-risk genotypes of MSR1 and ELAC2 in Caucasians and of RNASEL and MSR1 in Hispanics showed synergistic effects and suggest that an interaction between both genes in each ethnicity is likely to confer prostate cancer risk. Our findings corroborate the involvement of ELAC2, MSR1, and RNASEL in the etiology of prostate cancer even in individuals without a family history.
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PMID:Single and multivariate associations of MSR1, ELAC2, and RNASEL with prostate cancer in an ethnic diverse cohort of men. 2008 12

More and more studies have revealed that the level of serum prostate specific antigen(PSA) has little value for early diagnosis of prostate cancer (PCa). For example, negative prostate biopsies are as high as 70%-80% for patients with serum PSA ranging between 4 ng/mL and 10 ng/mL. However, the negative results cannot exclude the existence of cancer. In the studies of the early diagnosis of PCa, investigators focused on seeking biomarkers that have higher sensitivity and specificity. Recently, PSA derivatives, HPC1, PCA3, TMPRSS2: ETS, GSTP1, AMACR, GOLPH2, EPCA, sarcosine, and the combination of multiple biomarkers are widely discussed. In this article, we have reviewed their recent development and the prospective value of the combination of multiple biomarkers, which may be helpful for the early diagnosis and the prognostic monitoring of patients with PCa.
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PMID:Advances in biomarkers for the early diagnosis of prostate cancer. 2010 57


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